I. Suliman

Although the promise of cancer immunotherapy has been partially fulfilled with the unprecedented clinical success of several immunotherapeutic interventions, some issues, such as limited response rate and immunotoxicity, still remain. Metalloimmunotherapy offers a new form of cancer immunotherapy that utilizes the inherent immunomodulatory features of metal ions to enhance anticancer immune responses. Their versatile functionalities for a multitude of direct and indirect anticancer activities together with their inherent biocompatibility suggest that metal ions can help overcome the current issues associated with cancer immunotherapy. However, metal ions exhibit poor drug-like properties due to their intrinsic physicochemical profiles that impede in vivo pharmacological performance, thus necessitating an effective pharmaceutical formulation strategy to improve their in vivo behavior. Metal-based nanoparticles provide a promising platform technology for reshaping metal ions into more drug-like formulations with nano-enabled engineering approaches. This review provides a general overview of cancer immunotherapy, the immune system and how it works against cancer cells, and the role of metal ions in the host response and immune modulation, as well as the impact of metal ions on the process via the regulation of immune cells. The preclinical studies that have demonstrated the potential of metal-based nanoparticles for cancer metalloimmunotherapy are presented for the representative nanoparticles constructed with manganese, zinc, iron, copper, calcium, and sodium ions. Lastly, the perspectives and future directions of metal-based nanoparticles are discussed, particularly with respect to their clinical applications.

Cancer immunotherapy has revolutionized clinical cancer treatments by taking advantage of the immune system to selectively and effectively target and kill cancer cells. However, clinical cancer immunotherapy treatments often have limited efficacy and/or present severe adverse effects associated primarily with their systemic administration. Localized immunotherapy has emerged to overcome these limitations by directly targeting accessible tumors via local administration, reducing potential systemic drug distribution that hampers drug efficacy and safety. Sustained-release formulations can prolong drug activity at target sites, which maximizes the benefits of localized immunotherapy to increase the therapeutic window using smaller dosages than those used for systemic injection, avoiding complications of frequent dosing. The performance of sustained-release formulations for localized cancer immunotherapy has been validated preclinically using various implantable and injectable scaffold platforms. This review introduces the sustained-release formulations developed for localized cancer immunotherapy and highlights their biomaterial-based platforms for representative classes, including inorganic scaffolds, natural hydrogels, synthetic hydrogels, and microneedle patches. The design rationale and other considerations are summarized for further development of biomaterials for the construction of optimal sustained-release formulations.

AIM: There are many surgical techniques that deal with external rectal prolapse but perineal procedures have the advantage of reduced invasiveness. Therefore, despite concerns regarding high recurrence rates, the technique is still used by many surgeons. METHOD: This manuscript and video describe our early clinical experience using the Harmonic scalpel in 11 consecutive patients who underwent a Delorme's procedure for external rectal prolapse. RESULTS: The median age of patients was 76 (range: 30-94) years. There were no intra-operative complications, and the median operative time was 78 min. Intra-operative blood loss was minimal (mean 45 ml; range 20-70 ml). Median length of stay was 2 (range: 0-8) days. Overall morbidity and recurrence were both 18%, with a median follow-up of 15 (range: 1-23) months. Nine patients were operated on by a senior trainee with consultant supervision. CONCLUSION: The advantages of this device are mainly those of ease of mucosal dissection, minimal blood loss and shorter operative time in comparison with published series.